Nonsteroidal antiinflammatory drugs (NSAIDs) for chronic pain are preferable to opioids for a number of reasons. However, there are still concerns about adverse effects, including gastric ulcers, protein-losing enteropathy, nephrotoxicosis, and coagulation disorders. This study evaluated the long-term safety of several frequently used NSAIDs. Thirty-six dogs were evenly divided into 6 groups; each group received 1 of 6 daily oral treatments for up to 90 days: lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), ketoprofen (2 mg/kg for 4 days; then 1 mg/kg daily thereafter), or flunixin meglumine (1 mg/kg for 3 days, with consecutive 4-day intervals). Complete examinations, including clinical and laboratory tests (complete blood count, platelet count, serum biochemical analysis, urinalysis, bleeding and clotting times, and occult blood in feces) were conducted before treatment and on days 7, 30, 60, and 90. Gastroscopy was performed before and at the end of treatment. The authors conclude that all of the NSAIDs studied induced only minor, clinically unimportant changes in hemostatic and serum biochemical variables. Regarding gastrointestinal (GI) effects, lesions were found in half of the ketoprofen-treated dogs, but no adverse effects were noted at a lower dosage of 0.25 mg/kg Q 24 H for 30 days. Further studies would be needed to confirm the analgesic effectiveness of this lower dose. In the current study, 4 of 6 dogs given etodolac at this dose (highest recommended dose) had occult blood in their feces after 7 days. From the adverse GI effects in this study, the authors believe flunixin meglumine should be restricted to postoperative use only. Carprofen (4.0 mg/kg; recommended dose 4.4 mg/kg) induced the lowest frequency of GI adverse effects, followed by meloxicam. The authors advise that periodic complete blood count, serum biochemical analysis, and endoscopy be performed to monitor for adverse effects in dogs being treated long term with NSAIDs.

COMMENTARY: Despite the limitations of this study, it illustrates that NSAIDs of all classes should be used with appropriate caution and clinical monitoring, particularly with more extended administration of weeks to months. Carprofen induced the lowest frequency of GI side effects in this study out to 90 days; however, further trials are needed to examine adverse effects with long-term administration of this or other NSAIDs for months to years.

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Luna SPL, Basilio AC, Steagall PVM, et al. AM J VET RES 68:258-264, 2007.